Metal salt aminoalcohol complexes



United States Patent 2,999,872 METAL SALT AMINOALCOHOL COMPLEXES W E Craig, Philadelphia, and John ON. Van Hook, Abington, Pa., assignors to Rohm & Haas Company, Philadelphia, Pa., a corporation of Delaware N0 Drawing. Filed Mar. 6, 1958, Ser. No. 719,509 9 Claims. (Cl. 260-429) The present invention relates to a novel series of metal salt-aminoalcohol complexes which exhibit outstanding fungicidal properties.

At least four factors are important in determining the suitability of a given compound as a fungicide, namely, high fungitoxicity against a broad spectrum of fungi, good tenacity, low phytotoxicity against the plant host, and good stability. The necessity for high fungitoxicit'y against a broad spectrum of fungi is obvious, but the three other factors are also of very real importance in determining the economic suitability of a given fungicide. Some compounds otherwise suitable as fungicides are deficient in tenacity, thus they are expensive to use because of their fugitive nature and the necessity for repeated applications. Other compounds, while exhibiting -a high degree of fungitoxicity, cannot be used because they are also highly phytotoxic, causing serious damage to plants treated therewith. it has been found that some compounds exhibit suitable fungicidal activity when employed indoors under laboratory or greenhouse conditions, but exhibit appreciably less and economically unsatisfactory fungicidal activity when employed under field conditions. Further studies have revealed that this difference in indoor and outdoor activity is due to the destruction of the compounds under field conditions by ultraviolet light.

While the foregoing discussion pertains specifically to fungicides for use on plants, many of the criteria discussed above are also pertinent when assessing the value of compounds for broader use as general purpose fungicides. Thus for the protection of porous fibrous substrates, such as fabric, paper, belting, leather, etc., against fungal growth, chemical stability, and stability to ultraviolet light are also important properties, In many cases,

water-insolubility is required in those applications in which permanence is important.

*In accordance with the present invention, it has been surprisingly found that the ultraviolet stability of certain higher molecular weight aminoalcohols can be sharply increased by forming the complex of the aminoalcohol with certain metal salts. The metal salt aminoalcohol complexes of the present invention exhibit an excellent balance of the important properties necessary for a good fungicide, being highly fungitoxic, exhibiting good tenacity, showing low phytotoxicity, and being highly resistant I to decomposition by the action of ultraviolet light. The water solubilities of these compounds are also of a-low magnitude.

The compounds of the present invention are represented by the following structural formula:

f: CHr-N-Cdlm-OH X 2 R1 V in which M is a divalent metallic ion selected from the group consisting of nickel, cobalt, cadmium, 'zinc,'and copper, R is alkyl containing from four to eighteen carbon atoms, R is selected from the group consisting of hydrogen and lower alkyl, R is selected from the group consisting of hydrogen and lower alkyl and -hydroxyethyl, X is an anion, n is 2 to 3, Y is the valence of the anion X, and V is an integer of from 1 to 2, i.e., l or 2.

As is known in the art, the aminoalcohols employed as 2,999,872 Patented Sept. 12, 1961 ice intermediates in the preparation of the higher molecular weight complexes of the present invention can be prepared by a variety of methods. For example, they can be derived advantageously from olefins by reactions such as:

(a) Reaction of the olefin with hypochlorous acid followed by reaction of the addition compound with an amine as shown in the following equations:

-HC1 CICHrCHaOH-l-RsNH: RaNH-CHg-CEaOH (b) Epoxidation of the olefinfollowed by reaction of the epoxide with an amine as shown in the following equations:

Catalysts CHFCHH-Hzl): CHr-e-CH:

Or7CHz+RsITHHR3NHCHr-CH:0H

0 To prepare the di(hydroxyalkyl) derivatives (in which R is -CH CH OH) it is necessary to react ammonia with two moles of chlorohydroxy alkane or with two moles of the epoxide.

These aminoalcohols can be further substituted .by-reaction with halides of the desired hydrocarbon substituents as shown in the following (X being a halide radical):

R1 The benzyl halides (R R C H CH X) of this illustration are readily made by chloromethylation of the appropriate substituted benzenes.

The preparation of the metal salt complexes of these higher molecular Weight aminoalcohols can be carried out using any one of several methods including the'following methods:

(a) Adding a solution of the metal salts to a solution of the aminoalcohol in an inert organic solvent.

(b) Mixing the metal salt and the aminoalcohol .without the use of solvent (when aminoalcohols me liquid).

The products obtained by method (a) vary in physical form depending on the particular amine and metallic salt employed. In some cases precipitates form on mixing the reactants. These can be removed by filtration and dried. In other cases the complexes are soluble'in the solvent used and the solid complexes can be obtained by evaporation of the solvent. In those cases in which the solvent employed is non-phytotoxic, the solution as such can be employed as the essential ingredient of fungitoxic compositions.

Method (b) generally produces oils or mixtures ofoils and crystals which can be dissolved in any suitable-nonphytotoxic solvent, emulsified in water, or compounded into dusts. for use as fungicidal compositions.

The preferred method of preparation of the above methods is method (a) in which the amine is dissolved in a lower alkanol, the metallic salt is dissolved in a; lower alkanol, and the two alcoholic solutions are mixed. -Preferred lower alkanols are methanol, ethanol and propanol.

'The order of addition is not critical, and although the stituents, preferably two methyl substituents.

' n-Penty 'aminoalcoholscan be varied widely and still produce the products ofthe invention, the preferred ratio is one mole of metallic salt to one or more moles of theaminoalcohol, the latter being determined by the value of V.

Particularly effective metal salt-aminosalcohol complexes of the present invention include "those in which .the'R; substituent of'the benzene "ring consists of'a branched chain alkyl, the branched. radicals being lower alkyls, i.e., alkyls containing one to .fourcarbon atoms, particularly methyl or ethyl, and preferably methyl. Within this definition of R a preferred class of alkyl substituents includes those in which the carbon atom linking the benzene ring bears two such lower alkyl sub- A particularly preferred class of such substituents is those in which =R contains eight to eighteen carbon atoms and the carbon atom attached to the benzene ring and each alternate carbon atom thereafter in the straight chain bear lower alkyl substituents, preferable methyl.

The following are cited as examples of substituents of the formula R 1,1-dimethylpiopyl 1,1,3-trimethylbutyl 1,1-dimethylbutyl 1 1,l,3,3-tetr-amethylbutyl 1,1-dimethylpentyl 1,1-diethylpentyl i 1,1,3,3-tetramethylpentyl n-Hexyl 1,1-dimethylhcxyl 1,1-diethylhexyl l,1,3,3-tetramethy1hexyl 1,l,3,3,5,5-hexamethylhexyl n-Heptyl l-methylheptyl 1,1,3,3,5,5-hexamethylheptyl n-Octyl 1, 1,3,3-tetramethyloctyl l,l,3,3,5,5,7,7-octamethyloctyl n-Decyl. 1,l,2,2-tetraethyldecyl 1,1,3,3.,5,5,7,7'octamethyldecyl n-Dodecyl 1,1,3,3-tetramethyldodecyl 1,1,3,3,5,5-hexamethyldodecyl n-Octadecyl 2,2,4-trimethylpentyl 2,2,-dimethy1hexyl Various anions are suitable as the anion portion of the divalent metallic salts of nickel, cobalt, cadmium, zinc,

and copper used in the preparation'of the new compounds of this invention. Anions such as chlorides, bromides, iodides, sulfates, nitrates, phosphates, selenates, citrates, formates, acetates, and propionates can be employed, since it appears that the anion portion of the complex does not measurably aifect the fungicidal activity of the complex. 'The preferred anions are the chlorides, bromides, sufates, nitrates, and acetates, since such metallic salts exhibit good water and lower alkanol solubility. The chlorides, sulfates, and acetates of the desired'metals are mostcommonly' employed because of their high solubilities and ready commercial availability.

The compounds of the present invention exhibit pronounced fungicidal activity as shown by the control of a large number of fungi such as those responsible for late blight of tomatoes, .gapple. scab, and bean rust. furthermore, they exhibit high fungitoxicities against such typical 7 .fungi as Stemphylium sarcinaeforme and Monz'linia fructicola.

The compounds of the present invention can be formulated into fungicidal preparations employing methods well known to those skilled in the art. In the preparation of sprays for agricultural or horticultural use, the compound may be dissolved in a petroleum solvent such as xylene or a mixture of solvents, together with an emulsifying agent which permits dispersion of the fungicidal preparation in water. Dusts may be prepared by taking up the compound, after dissolving in petroleum solvent, with a finely divided solid, such as magnesium carbonate, talc, prophyllite, clay, magnesim aluminum silicate or other acceptable carriers. Wetting agents, sticking agents or dispersing agents may be used in such sprays and/ or dusts. i

A typical composition suitable for use as an agricultural spray may be prepared by dissolving 25 parts of bis[N -(2 hydroxyethyl) 4 (l,l,3,3,5,5 hexamethylhexyl)benzylamine] nickel (1i) chloride in parts of an aromatic solvent such as xylene. This solution becomes self-emulsifying on'the' addition of 5 parts of Triton WK-1339 (as described in Example 1, US. Patent 2,454,541). Good fungicidal activity was demonstrated under field conditions when used at the rate of 2 pounds active ingredient per acre.

Dusts may contain about one to ten percent of one or more of the metal salt aminoalcohol complexes, above defined. A typical composition is as follows:

5 parts metal salt aminoalcohol complex '50 parts magnesium aluminum silicate (Diluex) 45 parts pyrophyllite Wettable powders are often times desired and may be formulated as follows:

' 25 parts metal salt-aminoalcohol complex 50 parts magnesium aluminum silicate (Diluex) V 24 parts clay 1 part Tamol N (condensed sodium naphthalene sulfohate-formaldehyde) Compound Name I (1) Bis[N' (2 hydroxyethyl) dodecylmethylbenzylamine] nickel (II) chloride. (2) BislN (Z-hydroxyethyl) -(1-n1ethylhepty1)benzylamine] nickel (II) chloride. (3) Bisgl-( g-hydroxyethyl)dodecylbenzylamine] nickel (II) cone. (4) Bis[N-(2-hydroxyethyl)dodecylmethylbenzylamine] cadmium (II)c ride. (5) [Ii-(g-Hgfioaryethyl)dodecylmethylbenzylamme] copper )c ori e. V (6) Bis[N-(2-hydroxyethyl)dodeeylmethylbenzylamine] Z1110 '(II) chloride. 7 s r (7) t- Bis[N' N -di (2-hydroxyethyl) do da cylmethylbenaylamme] nickelOIDchloride. a (8) Bis[N (2 -hydroxyethyl)dodecylmethylbeuzylamme] nickel (ll) nitrate. (9) Bislglbfl-ghydroxyethyl)dodeeylbenzylamme] copper (II) s as. (l0) BisfirYl-(Z-hydroxyethyl)octadecylbenzylamine] nickel (II) c on e. (11) [N-(Z-Hy oxyethyl)dodecylbenzylamine] copper (II) chloride.

TEST 1 fica1ly, 25 parts acetone was addedto 0.86 part of each plex per 100 gals. of finished spray. The formulations containing 0.5 lb. per 100 gals. test spray may be prepared by dilution of the above-finished spray.

In this test, individually potted tomato plants 4 to 5 inches tall (4-leaf stage) were sprayed to the point of run-ofi with the test compound. After the plants had dried they were inoculated with a spore suspension of Phyzophflzora infestans containing 30,000 sporangia per ml. The plants were immediately placed in an incubation cabinet held at 10-12 C. and 100% relative humidity.

After incubation under these conditions for 24 hours the plants were placed on a bench in the greenhouse and held for seven days, at which time each plant was ranked forthe percentage of leaf area infected.

Each treatment was replicated five times. The average rank reading was calculated according to the following system:

Percent leaf area infected =none l'=trace (one small lesion) 2=1-5% (few lesions) 3=6-17% A ranking below 2 is considered to be excellent. The results of this test were as follows:

In the fungitoxicity portion of this test, the method utilized is one standardized by the American Phytopathological Society, Committee on Standardization of Fungicidal Tests. All details of this test are presented on pages 627-632, volume 33 of Phytopathology, July 1943.

The series of dilutions for this test were prepared by dissolving 1 gram of each of the compounds identified below in 20 cc. of solvent and then adding 79 cc. of water to make a 1% solution of the compound. This stock solution was then serially diluted with water to concentrations of 0.1%, 0.01%, 0.001%, and 0.0005%. The solvents used with each of the compounds listed are identified in the following table:

A spore suspension of Monilinia fructicola (M.f.) or

' Stemphylium sarcianeforme (S.s.) in an amount of 0.5 cc.

was added to 2 cc. of each of the different serial dilutions and four drops of each of the resulting suspensions were pipetted onto individual cellulose nitrate coated glass slides. These slides were then placed in large Petri plates sealed with water and held at a constant temperature for a period of 16-24 hours, at which time the percentage of spores showing no germination was determined. This was done by counting 25 spores in the center of each of the four drops on each slide with the proper correction belng made for non-viable spores as determined by the control (untreated) slides in each chamber. Sfemplzylium sarcianeforme spores were standardized to 5,000 and Monilinia fructicola to 10,000 per ml. in these tests. The data obtained were then plotted on logarithmic probability paper and straight line curves were drawn by inspection. The LD values were determined by extrapolation. This value is the concentration at which 50% of the test spores would be prevented from germinating.

In the phytotoxicity portion of this test, individually potted tomato plants were sprayed to the point of run-elf with the test compounds at concentrations of 1%, 0.1%,

and 0.01% active ingredient. The plants were immediately placed on a bench in the greenhouse after treatment. Each treatment was replicated three times. At the end of seven days each plant was ranked according to the system presented below for injury.

Injury rank on tomatoes 0=none .=slight. 2=moderate 3=severe 4=dead The results of these tests were as follows:

congmmd Fungitoxlcity Phytotoxieity v. Tomatoes at 55%?- g gfi g- 1% 0.1% 0.01%

(1)--- 5-10 5-10 0 0 0 1 10-50 3 o 0 5 1 4 0 0 5-10 5-10 2 0 o a) 5-10 10-50 1 o 0 (6)- 5 5 4 2 0 (7) 10-50 10-50 2 o 0 (8)- 1 1-5 4 1 0 (9). 5 -10 5 3 0 o (10)- 10-50 10-50 a o 0 (11) 5-10 5 0 0 0 TEST 3 An apple scab test was conducted as follows:

Individually potted apple whips (3 feet tall) were sprayed to the point of run-ofi with the treating agent (prepared as described in Test 1 above) and allowed to dry. They were then inoculated with an aqueous spore suspension (Venturia inaequalz's) and immediately placed in an incubation cabinet (100% relative humidity and 75 F.) After two days incubation in this cabinet they were moved to a. bench in the greenhouse and held there for three weeks. The percentage of leaf area showing infection was then estimated.

The results of this test were as follows:

Concentra- Percent of Compound No. tlon (lb/100 Total Leaf gal.) Arealniected 1 1.0 0. 5 O 0. 5 5.0 (7) 1.0 5.0 0.5 4. 5 Untr a9. a

The examples appearing hereinafter are for the purpose of illustrating the preparation of various active complexes of the present invention. In these examples, the reactions are carried out at room temperature and the parts employed are parts by weight.

EXAMPLE I Bis [N (Z-hydroxyethyl -4-(1 ,1 ,3,3,5 ,5 -hexamethy lhexyl berizylamine1nickel (11) chloride A solution of.5l.1 parts (0.16 mole) of N(2-hydroxy- 75 ethyl)-4-(l,1,3,3,5,5 hexamethylhexyl)benzylamine in 7 33.2 parts of ethanol added to a solution of 10.0 parts (0.08 mole) of nickel chloride hexahydrate in 89.6 parts of ethanol yields the above compound in solution. The compound can be isolated from solution by distilling off the solvent.

- i EXAMPLE H p t Bis [N (Z-hydroxyethyl) -4-oczadecylbenzylamine] (II) chloride v 7 V A solution of 19.2 parts of N(2-hydroxyethyl)-4octadecylbenzylamine in 190 parts of'ethanol added to 'a solution of 5.9 parts of nickel chloride hexahydrate in 25 parts of ethanol obtains the above compound in solution.

EXAMPLE HI Bis [N (Z-hydroxyethyl -5 -(1 ,1 3,3,5 ,5 -hexam ethylhexyl Z-mezlzylbenzylamine]'nickel (ll) 'chloride' A solution of 33 parts of N(2-hydroxyethyl)-5-( 1,1, 3,3,5,5 hexamet ylhexyl) 2 methylbenzylamine in 50 parts of ethanol added to a solution of 11.8 parts of nickel chloride hexahydrate in 50 parts of ethanol yields solution of the above compound.

: EXAMPLE Bis[N,N-di(2-hydr0xyetliyl)-5-'(1,1,3,3,5,5-hexamethylhexyl)-2-mezhylbenzylamine] nickel (II) chloride Asolution of 75.4 parts of N,N-di(2-hydroXyethy1) -5- l,1,3,3,5,5-hexamethylhexyl) 2 methylbenzylamine in 100 parts of ethanol added to a solution of 23.7 parts of nickel chloride hegrahydrate in 100 parts of ethanol obtains the above compound as a precipitation cooling.

Bis[N (S-hydroxy pro pyl -4-(1 ,1 3,3,5 ,5 -he x ainihylhexyDbenZyZamine] nickel (II) chloride A solution of 33.5 parts of N(3-hydroxypropyl)5?l-(1,

1,3,3,5,5-he: iamethylhexyl)benzylamine in 50 parts of.

- thanol ddedto a s on o .-8..P@Il 9 Ii K ride hexahydrate in 50 parts of ethanol yields a solution of the above compound which, upon removal of the ethanol, is an amorphous material.

EXAMPLE VI Bis[N (Z-hydroxyethyl) -4-octadecylbenzylamine] zinc (II) nitrate A solution of 32.2 parts of N(2-hydroxyethyl)-4octa- .decylbenzylamine in 100 parts of methanol added to a solution of 11.9 parts of zinc nitrate in 100 parts of methanol yields the above complex readily at r oom temperature. t

. EXAMPLE VH Bis[N(2-hydroxyethyl)-4-.(IQniethyIhepIyDbenzyI:

amine] cobalt (I1) acetate A solution of 5.29 parts of N(2-hydroxyethyl)-4-(lmethylheptyhbenzylamine in 100 parts of .propanoluadded i to a solution'of 2.49 parts ofpobalt acetate in 20 parts- .EXAMPQDQ 7 Bis [N (Z hydroxyethyl) 5-octadecyl-2-inethylbenzylamine] copper (1]) su lfate A solution of33.4 parts of N(2-hy dronyethyll 5-octa decyl-Z-methylbenzylamine "in 100, parts of methanol added to a solution of 9.96 parts of copper sulfate in parts of methanol yields theabove compl egcimmediately.

. 'JEXAMPLEXU H Repeating the process as set forth in Example I by substituting 0.08 moleof each of nickel bromide, nickel nitrate, nickel sulfate, nickel citrate and nickel acetate for the nickel chloride obtains complexes with the sub stituted salts whichexhibit satisfactory fungicidal activity. r r EM V V V t.

Bis[N-(Z-hydroxyethyl)-2-butyl 5-octylbehzylamine]zinc (II) bromide 3 A solution bf 31.9mm; of N-(zii dmx etn ij-z butyl-S-octylbenzylamine inlOO parts of ethanol added to a solution of 11.3 parts'of zinc bromide in 100 parts of ethanol forms a soluble complex which maybe isolated by evaporation of the solvent.

EllAL/lPLE 7 Bis [N- (2-hydroxyethyl)-N-methyl;; hutylbenzylamine] cadmium (11) nitrate A solution of 22.1 partstof N- (2 -liy droxyethyl)-N- methyl-4-butylbenzylamine in 5Q parts;ot methanol added to a solution of 15. 4 parts of cadmium nitrate tetrahydrate in 100 parts of methanol obtainslthe, above complex.

EXAMPLE X111 ,.f N(2-h dmxyezhyl) 2.5;dizutyl zy a copper (11),.clz loride Y Y Y 5 ditrbutyl nzyl m qe -3 parts) poured onto 13.5 parts of powdered copper chloride and stirred at" 100 C. :until the'jjcopper chloride dissolves yields the desired complexapiwn The foregoing description of the present invention,

including the. examples,1 is for the purpose of illustration and is not limiting to the scopeof the invention;

Weclaim: V 1. A compound of the formula, V a R2 7 V w t R: M @om-iemm-on x 2, r vi wherein M is, a divalent metallic ion selected fromthe group consisting of nickeL'cobalt, cadmium, zinc and copper, R is alkyl containing from-four to eigliteen carbon atoms, R is selected from the group consisting of hydrogen and lower alkyl, R is selected from the group consisting of hydr66fifloWef alkyl andZ-hydroxyethyl, X is'an anion selected from thegroup consisting of halide, sulfate; nitrate, hosphate; "selenate, fcitrate, andlovier a1kanoate, n" is"'aii'int'e'g'er"of'from 2 to 3, Y is the Yfllolilo e1 th'anioirX," and"V"i's'"an integer of from 1 to} V .i

2. A compound as set fofth'inclaim"l'in which the benzene ring carbon atom" "of "R1 and each alternate carbon aton thereafter in'tlie strai'ghtchain of R a e er. lky1u st tfi 3. A compound as setforthin clean-in which the lower alkyl substituents are methyl groups;

' 4. A compound as "set forthin claim-1 injwhich the benzene ring linking carbon atomiofR has two methyl substitutents. I

5 ,A compound as set forth inclaim lin which the divalent metallic ion is copper. a

6. A compound asset forth in claim 1 in which the .divalent metallic ion is nickel. i e 'i s 10 7. A compound as set forth in claim 1 in which the References Cited in the file of this patent divalent metallic ion is cobalt. F

8. A compound as set forth in claim 1 in which the UNIHFD STATES PATENTS divalent metallic ion is inc Gmltter 9. A compound as set forth in claim 1 in which the 5 2,798,102 schaefier at July 2, 1957 divalent metallic ion is cadmium 2,867,566 Weinberg Jam 1959 

1. A COMPOUND OF THE FORMULA 